One in three community dwelling people over age 65 and one in two over age 80 fall each year. The consequences of falls among older adults are often devastating, resulting in loss of independence, institutionalization and premature mortality. Falls also are responsible for greater than 20 billion dollars a year in healthcare costs in the United States. Although many fall prevention strategies targeted against clinical risk factors have been tested, their success in reducing falls has been modest. Current falls research in aging is mostly focused on clinical predictors of falls and there is a knowledge gap regarding underlying biological and neural mechanisms of falls. Emerging evidence from our and other studies implicates biological derangements in inflammation, oxidative stress, and vascular pathways in the occurrence of disorders of gait, balance, and cognition, which are major risk factors for falls in older adults. We hypothesize that abnormal biological pathways initiate atherosclerosis leading to cerebral vascular damage that increases risk of falls in older adults. We draw together a multidisciplinary team to conduct high-quality research to establish biological and neural mechanisms of falls building on our extensive cognitive and mobility research. We will cross-enroll 530 participants, age 65 and older, from the ongoing Central Control of Mobility in Aging study offering a cost and time efficient strategy to study biological and neural mechanisms of falls. This proposal will employ rigorous clinical assessments, many developed and validated in our other aging studies, to assess fall risk. We propose the following three synergistic aims focusing on our common theme of biological and neural contributions to falls in aging. 1). Determine biological mechanisms (inflammation, oxidative stress, and vascular pathways) contributing to falls. 2). Establish contributions of central microvascular pathology to fall risk using state of the art neuroimaging techniques. 3). Establish the contribution of the prefrontal cortex to falls using an innovative functional near infrared spectroscopy (fNIRS), that enables imaging during walking. While biological risk factors for falls are potentially modifiable, the paucity of data is a critical barrier for translation to clinical interventions. While many fal prevention strategies targeted against clinical risk factors have been tested, their success in reducing falls has been modest in research settings and even less so in the real world. A deeper understanding of underlying biological mechanisms and neural substrates for falls may lead to more efficient risk identification and improve the effectiveness of current interventions for fallsin older adults.